Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study

Abstract

The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

“…(Polito & Liknaitzky, 2022). In short, microdosing leads to perceivable effects, explaining why CGR is universally high across trials (Cavanna et al, 2022;Murray et al, 2021;Szigeti et al, 2021;van Elk et al, 2021), but at this point none of these effects seem to be related improved mental health and the other hypothesized benefits. If our hypothesis is correct, then, either improved blinding or a sample without positive expectancy would nullify the observed benefits of microdosing by nullifying AEB.…”

“…We hope that microdosing will have a positive scientific legacy despite the mostly negative results in current trials (Cavanna et al, 2022;de Wit et al, 2022;Marschall et al, 2021;Szigeti et al, 2021) by forcing the research community to address its blind spot for blinding integrity.…”

“…This feature is represented by the arrow between the treatment (TRT) and perceived treatment (PT). The strength of this relationship is encoded by µ 𝑆𝐸 , which is the average probability increase of guessing active treatment after receiving active treatment, the default parameter value was chosen such that simulated trials have CGR~0.7, which is consistent with both microdosing (Cavanna et al, 2022;Szigeti et al, 2021) and antidepressants (Margraf et al, 1991;Rabkin et al, 1986;Riddle & Greenhill, 2007).…”

“…Anecdotal claims have been made that microdosing improves well-being and cognition (Fadiman & Korb, 2019;Winkelman & MD, 2019). Observational studies have generally confirmed the positive anecdotal claims (Anderson et al, 2019;Kaertner et al, 2021;Polito & Stevenson, 2019;Rootman et al, 2021), but placebo-controlled studies have failed to find robust evidence for larger than placebo 3 efficacy (Cavanna et al, 2022;de Wit et al, 2022;Hutten et al, 2020;Szigeti et al, 2021;Yanakieva et al, 2019).…”

A long trip into the universe: Psychedelics and space travel

“…Over the last decade, "microdosing" or sub-psychedelic, small and regular dosing of psychedelics, has attracted a significant amount of public interest with anecdotal reports of positive socio-affective, cognitive, and physical outcomes. However, it should also be noted that the current, peer-reviewed evidence-base does not provide sufficient support for the application of microdosing as a health and wellness promotion strategy in long-duration space travel (Cameron et al, 2020;Cavanna et al, 2022).…”